Controlling antibiotic release from mesoporous silica nano drug carriers via self-assembled polyelectrolyte coating

Mesoporous silica nanoparticles (MSNs) have been explored as controlled drug delivery systems since the early 2000s, but many fundamental questions remain for this important application. We sought to design a pH controlled delivery system of gentamicin, an aminoglycoside antibiotic, based on MSNs. Under optimal conditions, MSN was able to load 219 µg gentamicin per mg MSNs. Polymeric networks encompassing gentamicin loaded MSNs were then established to tune the release kinetics. Embedding of drug pre-loaded MSNs was performed by an efficient layer-by-layer (LbL) self-assemble strategy using polystyrene sulfonate (PSS) and poly (allylamine hydrochloride) (PAH). We characterised the release kinetics by nonlinear mixed-effects modelling in the S-ADAPT software. The mean release time from uncoated MSNs was 3.6 days at pH 7.4 and 0.4 days at pH 1.4. A further slower release was achieved by diffusion through one or two PSS/PAH bilayer(s) which had a mean transit time of 6.0 days at pH 7.4 and 3.5 days at pH 1.4. The number of bilayers affected the shape of the release profile. The developed nano-drug carriers combined with the self-assembled polyelectrolyte coating allowed us to tune the release kinetics by pH and the number of bilayers.